Design Finalization for Virus Safety

Step 6

Once the virus clearance step has been optimized and virus retention studies completed, your next challenge is designing a strategy that enables you to increase your flow volumes within the constraints of your physical plant, without violating the safety margins you have established for your project.

A key decision is finding a filter configuration that will support a large-scale implementation. When multiple filters are required to process the batch volume you have set, look for a filtration solution that can be installed to meet your process time requirements and to meet the physical constraints of your plant. Merck can help increase your probability of success with Procedural reviews, Operator Training, Equipment Qualification and our knowledge in standard approaches and expertise in downstream processing.

Plant Related Considerations:

Sanitization

Hardware requirements

Disposable flow path opportunities

Operating Procedure Related Considerations:

SOP feasibility

Equipment and operator qualification

Automated and or Manual Integrity testing

Design Constraints:

Ability for increased batch size

Safety Factors

Tolerance for process excursions

Other virus filter-related considerations include:

Operating sequenceA typical sequence of operations in a virus filtration process includes the following steps:

Sanitization and sterilizationIn a typical downstream purification process, virus clearance filters are used downstream of a chromatography column and upstream of an ultrafiltration/diafiltration step, neither of which is considered an aseptic operation. However, there appears to be an industry trend to sanitize or sterilize the virus filter to reduce the bioburden. Some virus filters are available pre-sterilized, thus eliminating the sterilization step. It is important that the filters you select are compatible with the sanitization or sterilization method you plan on implementing at manufacturing scale, and that the process steps used during large scale processing are also carried out during your scaled down virus retention studies.